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Associations between modifiable health risk factors during middle age with disability and mortality in later life are critical to maximizing longevity while preserving function. Positive health effects of maintaining normal weight, routine exercise, and non-smoking are known for the short and intermediate term. We studied the effects of these risk factors into advanced age.
A cohort of 2,327 college alumnae ≥60 years was followed annually (1986–2005) by questionnaires addressing health risk factors, history, and Health Assessment Questionnaire disability (HAQ-DI). Mortality data were ascertained from the National Death Index. Low, medium, and high risk groups were created based upon the number (0, 1, ≥2) of health risk factors (overweight, smoking, inactivity) at baseline. Disability and mortality for each group were estimated from unadjusted data and regression analyses. Multivariable survival analyses estimated time to disability or death.
Medium and high-risk groups had higher disability than the low risk group throughout the study (p<0.001). Low-risk subjects had onset of moderate disability delayed 8.3 years compared with high-risk. Mortality rates were higher in the high risk group (384 versus 247 per 10,000 person-years). Multivariable survival analyses showed the number of risk factors to be associated with cumulative disability and increased mortality.
Seniors with fewer behavioral risk factors during middle age have lower disability and improved survival. These data document that the associations of lifestyle risk factors upon health continue into the ninth decade.
Improvement in health in the United States has resulted in greater longevity, raising concerns about increased frailty and disability in an increasingly aging population1,2. Potential consequences of increasing age-related disability include higher health costs and decreased quality of life. Alternatively, if reduction in health risks postpones disability to a greater degree than it extends life, health burdens of age may decrease3. We sought to examine the hypothesis that health gains associated with fewer health risks would continue through the ninth decade of life.
Behavioral risk factor reduction is a potentially cost-effective means to improve long-term health outcomes. Most studies have evaluated risk factors individually rather than as a summation4–7. Few have followed subjects into advanced age, essential for estimation of cumulative lifetime health.
In 1998, we reported our eight-year experience on the relationship of health-related risk factors to cumulative disability in a cohort of University of Pennsylvania alumni from 1939–1940. We found that fewer health-related risks (smoking, overweight, and inactivity) led to increased survival and decreased disability11. The relative improvements in death rates and disability incidence could not be reliably estimated given relatively few deaths and young age of 68 among survivors. Here, we examine the long-term associations of cumulative risk factors upon disability and mortality to an average age of 85 years with nearly 50% mortality.
In 1986, we initiated a longitudinal study of risk factors for progressive disability and mortality in a previously identified cohort of college alumni12, inviting individuals from University of Pennsylvania alumni records in 1939 and 1940. Respondents (n=2843) were followed annually with mailed self-administered questionnaires11.
Participants averaged 68-years of age at baseline and had completed at least two consecutive questionnaires between 1986–2005 (n=2,327). The observation period for each participant was time from baseline questionnaire through death, last completed questionnaire, or end of the observation period, December 2005.
Self-reported data were collected on demographics, physical function, and selected risk factors. We chose body mass index (BMI), cigarette smoking, and physical inactivity as modifiable risk factors frequently associated with impaired functional status and premature mortality13–15. Health risk factors were defined at initial survey: (1) being above or below a normal weight range (abnormal BMI), defined by National Heart Lung and Blood Institute (NHLBI) guidelines16, as a BMI > 25 or < 18.5 kg/m2; (2) current cigarette smoking; and (3) inactivity, defined as absence of vigorous physical activity that works up a sweat (including jogging, cycling, brisk walking, swimming and other sports). Questionnaires captured data on the prevalence of comorbid conditions including hypertension, diabetes, arthritis, stroke, cancer, depression, cardiovascular, pulmonary, neurologic and gastrointestinal diseases. Subjects estimated walking pace using an ordinal scale: 1=casual or strolling (less than 2 mph); 2=average or normal (2 mph); 3=fairly briskly (3 mph); 4=brisk or striding (4 mph or faster).
Participants were placed into three risk groups based upon the number of baseline risk factors: low (no risk factors), medium (one risk factor), and high (≥ two risk factors). Primary outcomes were time to disability and death.
Disability was assessed by the Health Assessment Questionnaire Disability Index (HAQ-DI), a validated measure widely used in clinical studies17,18. It assesses functional ability in eight categories: rising, dressing and grooming, hygiene, eating, walking, reach, grip, and routine household activities18. Each is scored from 0 (no difficulty) to 3 (unable to do) after accounting for assistive devices or help of another person. The disability index averages the individual category scores, yielding a score from 0 to 3. For reference, a HAQ–DI of 0.25 is roughly equivalent to mild disability in 1–2 functional categories; 0.5 to moderate disability in two categories. Disability scores of 0.75 to 1.0 are typical of subjects with rheumatoid arthritis and osteoarthritis19–21.
We examined three disability endpoints: (1) HAQ-DI for each calendar year of observation; (2) cumulative disability over the period of observation (sum of annual HAQ-DI scores); and (3) time to development of moderate disability (HAQ-DI=1).
Mortality data for all study participants through 2005 was ascertained using the National Death Index22.
Baseline characteristics were compared using means and proportions. Because some comorbidities are singular events (stroke, myocardial infarction) and may not be reported on subsequent questionnaires, baseline and cumulative prevalence was tabulated. Unadjusted mean baseline HAQ-DI scores were compared by study group. Similarly, annual and cumulative disability scores in low-risk subjects were compared to medium- and high-risk groups using Student t-tests. Kaplan-Meier curves were used to compare time to first HAQ-DI=1.0 (moderate disability) and mortality between groups. Multivariable Cox proportional hazard models were created for the development of moderate disability and time to death to control for variables known to affect outcomes (age, gender, baseline disability, walking pace23, and comorbidities). Time to moderate disability and to mortality was estimated both from the unadjusted data and from linear regression of all data points.
To understand the relative roles of each risk factor (overweight, smoking, and inactivity), we constructed multivariable Cox proportional hazard models using each separate risk factor as covariates. Given that higher baseline HAQ-DI scores are strongly correlated with both future disability and mortality24,25, we performed these analyses on the subset of participants with zero baseline disability (n=1,736, 75% of subjects). Models were adjusted for age, gender, walking pace, and comorbidities.
Population attributable risk (PAR) for mortality and for moderate disability (HAQ-DI=1) was calculated for each individual risk factor as well as for individuals with ≥ 1 risk factor. PAR were calculated separately for the entire cohort, subjects with baseline HAQ-DI=0, and for survivors with baseline HAQ-DI=0. Analyses were performed with SAS [Carey NC]; a two-sided test with p<0.05 was considered statistically significant. This study received IRB approval and all participants provided written informed consent.
At baseline, participants had a mean age of 68 years and were predominately Caucasian and male as expected from university alumnae in 1939–1940. Mean BMI was 24.7kg/m2; 41% (n=985) had a BMI>25kg/m2 and 1.3% (n=31) <18.5kg/m2. Eight percent (n=190) smoked; 52% (n=1,213) were inactive. Pair-wise correlations between overweight and inactivity were −0.07 (p=0.34) among smokers and −0.06 (p=0.006) among nonsmokers.
Risk groups were composed as follows: Low (n=605, 25.9%); Medium (n=1,073; 46.1%); High (n=649; 27.9%). Cohort characteristics by risk group at baseline and last follow-up are shown in Table 1. Risk groups were comparable in gender, ethnicity, baseline age and years of education.
By definition, low-risk participants met healthy BMI, smoking, and physical activity criteria at baseline. Medium-risk participants had a very low smoking rate (<5%); 41% had an abnormal BMI; and 55% did not exercise routinely. In contrast, 22% of high-risk subjects smoked, 89% had abnormal BMI, and only 3.5% exercised routinely. Walking pace was slower in the medium and high-risk groups when compared to the low-risk group. Baseline rates of hypertension, pulmonary disease, gastrointestinal disorders, arthritis and diabetes were higher in the high-risk compared to low-risk group. Prevalence of comorbidities was similar between groups.
Baseline HAQ-DI scores were low for all groups, although medium- and high-risk groups had higher scores than the low-risk group. The majority (75%) of participants had no disability. By the last observation, risk factor differences between groups had attenuated; although all comparisons remained significantly different between risk groups. Walking pace decreased and cumulative prevalence of comorbidies increased for all groups. With the exception of higher rates of hypertension and diabetes among high-risk participants, the cumulative prevalence of comorbidies did not differ significantly between risk groups.
Participants were observed for an average of 15.6 years. Age of survivors in 2005 was similar for all groups (85 years). Last observed HAQ-DI scores were significantly lower for the low-risk group compared to medium- and high-risk groups. Forty-eight percent of all study participants had died by 2005. Although age at death was similar, mortality rates were nearly 50% higher for high- compared to low-risk participants (384 vs. 248 per 10,000 person-years, p<0.001). Approximately 1% of participants, excluding decedents, were lost to follow-up each year. Those participants were 6 months younger with similar lower baseline HAQ-DI Scores.
Figure 1 displays yearly HAQ-DI scores by risk group. Disability increased each year in all groups. Participants without risk factors had the lowest HAQ-DI at each time point, followed by those with one risk factor. Differences were most pronounced at the later time points.
Figure 2 shows the dose-response relationship among groups in cumulative disability when comparing all participants, survivors, survivors without baseline disability, and by gender. Differences are most pronounced when comparing high- to low-risk participants. Cumulative disability, a surrogate for total lifetime disability, contains a bias in favor of the high risk group because of the shorter period during which disability accumulates. Similar results were seen when average disability was compared. Decedents had the highest average disability scores at all time points.
We compared Kaplan-Meier curves for the time for each group to attain a HAQ-DI of 1.0 (moderate disability) and death. The median time to develop moderate disability was approximately 8.0 years longer in the low-risk than the high-risk group (log-rank test p<0.0001).
Cox proportional hazard models adjusted for age, sex, and baseline disability yielded nearly identical findings. Compared to low-risk, the high-risk group had nearly a two-fold increased risk for the development of moderate disability (HAQ-DI=1) (HR 1.91, 95%CI 1.50–2.42), while medium risk participants had a 60% increased risk (HR 1.61, 95%CI 1.29–2.01). Age (HR 1.11, 95%CI 1.08–1.13) and higher baseline disability (HR 49.5, 95%CI 37–66) were also associated with disability.
The unadjusted probability of survival was significantly higher for low- compared to medium-and high-risk groups (Figure 3). Curves separated early in the period of observation and continued to diverge over time. Sixty percent of the low-risk group was alive at 19 years compared to 53% and 43% in medium- and high-risk groups. The time to 20% mortality in each group was postponed by 3.6 years in low- versus high-risk participants; the postponement was 3.9 years to 40% mortality. Similar results were found when analyses were restricted to participants without baseline disability. Using survival analysis, medium- and high- risk participants had increased adjusted risks of mortality compared to low-risk (HR 1.18, 95%CI 1.01–1.37 and HR 1.47, 95%CI 1.25–1.73) although the differences were less marked compared with disability differences.
Multivariable Cox proportional hazards models were used to examine the relative role of each individual risk factor (abnormal BMI, smoking, and inactivity) as well as baseline walking pace and individual comorbidities upon moderate disability and mortality. Because the baseline HAQ-DI is among the strongest predictors of future disability and mortality, these analyses were restricted to the subset of participants (n=1,736) with baseline HAQ-DI=0 (Table 3). Males had an increased hazard of death (HR 1.47, 95%CI 1.18–1.81) but a reduced risk of disability (HR 0.52,95%CI 0.40–0.68). Among the three risk factors, smoking was associated with a two-fold increased risk of moderate disability (HR 2.02, 95%CI 1.32–3.08) and an even higher risk of death (HR 2.32, 95%CI 1.83–2.94). Faster walking pace was associated with a decrease in both morbidity and mortality. The presence of hypertension, diabetes, cardiovascular, pulmonary disease, stroke, or cancer at the baseline was associated with higher mortality; whereas only arthritis and stroke were associated with disability.
Since smoking as associated with the greatest risk for disability and mortality, we repeated the analysis on non-smokers (n=1,595). Neither having an abnormal BMI nor inactivity was significantly associated with disability or mortality in this smaller subset. Comorbid conditions and walking pace had similar effects upon disability and mortality in non-smokers.
Because of the possibility that death may be related to disability, and as such could present informational censoring over time26, we repeated multi-variable proportional hazards modeling for disability among the 960 survivors. The magnitude of hazard ratios for covariates including individual risk factors, walking pace, and comorbidities was not substantially different than when decedents were include in the analysis (data not shown).
Population attributable risk for mortality and for moderate disability (HAQ-DI=1) were calculated for each risk factor and for individuals with ≥ 1 lifestyle risk factor (Table 4). Excess risk was seen for all risk groups for both mortality and moderate disability. Similar to the survival analysis, the highest attributable risk was seen with smoking.
This longitudinal study of 2,327 college-educated older adults shows that maintaining normal weight, not smoking, and regular physical activity are persistently associated with slower development of disability and reduction in mortality. Results are consistent across different subgroups of the cohort: men, women, those with and without initial disability, decedents, and survivors; and across analytic methods. The differences among subjects with zero, one, and ≥ two risk factors appeared early and were constant or diverged further as participants approached an average age of 85. Results did not differ substantially with subgroup analyses. As individual behavioral risk factors, only smoking appeared to have a statistically significant association with both disability and mortality after controlling for the prevalence of comorbid conditions at enrollment. The postponement of mortality was 3.6 to 3.9 years, similar to the roughly four years expected from the Gompertz function for an increase of 50% in mortality rates27.
Our findings support previous studies of aging in older adults and provide a longitudinal context, a longer period of observation with extension into the ninth decade, essential for estimation of cumulative lifetime morbidity. Several studies have documented independent effects of lack of physical activity and weight above the normal range as risk factors for increased disability and mortality in older adults28–31. Although the role of cigarette smoking on increased mortality is well established, there are fewer data regarding cigarette smoking and physical disability7,32. A systematic review of behavioral determinants of healthy aging identified not-smoking, ongoing physical activity, and maintaining normal weight as key elements leading to improved outcomes in aging individuals33. Indeed, population-based studies of the United Kingdom found that smoking was directly attributable to 19% of all deaths and 12% of disability adjusted life years (DALY) lost34. Similarly, physical inactivity was found to be responsible for 3.1%35 and overweight contributed to 7.3%36 of morbidity and mortality in the UK. Because of differences in populations between studies, direct comparisons to results seen in this cohort (college-educated older adults) to the UK population is difficult, although results are similar with respect to smoking contributing to the highest risk for both death and disability.
Our study was not designed to address the mechanisms underlying associations between behavioral risk factors and disability and mortality. We can speculate that such mechanisms include accrual of comorbid conditions such as cardio-pulmonary disease and diabetes as described in other studies of similar populations34–36. Although our study did not find striking differences in the cumulative prevalence of comorbid conditions between risk groups as subjects entered advance old age, it is possible that the severity of these conditions, earlier age of onset, as well as differences in cardio-respiratory reserve explain our findings.
The strengths of this study include the large cohort followed annually for nearly two decades into their mid 80s. This cohort had little to no baseline disability in their seventh decade of life, allowing cumulative disability to be estimated.
Several limitations need to be considered. With the exception of death, data were acquired from self-report. However, we have documented in similar populations a strong correlation between HAQ-DI scores and observed performance37.
Loss to follow-up is to be expected in studies of long duration, but has the potential to introduce bias if living participants who are lost-to-follow up are substantially different from completers. We had a low rate of loss (<1% per year), but with slightly higher rates of drop-out among low-risk participants. Completers were similar, if not slightly older, than survivor lost-to-follow-up. Mortality data were ascertained irrespective of completer status.
We approached the issue of informational censoring of death in this study by several means. First, we analyzed determinants of death and disability separately among all participants. When analyzing disability outcomes, for which death may be associated with disability, cumulative disability among all participants and compared that to the subset of surviving participants. Similar approaches were employed when analyzing risk factors for the development of disability.
This study was initiated as a test of the Compression of Morbidity hypothesis3, where fewer health risks would postpone both morbidity and death, but morbidity more so than mortality. Data presented here are consistent with that hypothesis, with mortality postponed nearly four years and disability to the 0.3 level (the highest with complete data) postponed by 8.2 years. There are, however, several challenges in making direct comparisons of morbidity and mortality. Disability is a subset of morbidity and the degree to which it is a valid surrogate for morbidity might be challenged. Second, these data, even after two decades, only contain the first one-half of deaths and much of the morbidity will come after age 85. It may be speculated that differences between risk groups will narrow in the future, though at this point differences continue to diverge. Direct comparisons, therefore, should be made with caution.
Study of disability trajectories in the last months of life suggests little relation between specific disease diagnostic categories or counts of co-morbid diseases and disability levels, implying that population movement toward trajectories with later onset of disability, irrespective of diagnoses, could improve senior health38. Our findings that health risk factors in the seventh decade of life continue to predict disability and mortality in the eighth and ninth decades suggest that maintenance of healthy lifestyle behaviors may help compress morbidity far into the lifespan. This study provides support for health policy approaches that postpone morbidity through lifestyle risk reduction.
Funding Source: This study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR43584)
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Conflicts of Interest: None
All authors had full access to the data, and each contributed substantially to writing and revising the manuscript